This study aims to explore whether Naoxintong Capsules improve multiple cerebral infarctions and myocardial injury via promoting angiogenesis, thereby exerting a simultaneous treatment effect on both the brain and heart. Male SD rats were randomly divided into six groups: sham-operated group, model group, high-dose, medium-dose, and low-dose groups of Naoxintong Capsules(440, 220, and 110 mg·kg~(-1)), and nimodipine group(10.8 mg·kg~(-1)). Rat models of multiple cerebral infarctions were established by injecting autologous thrombus, and samples were collected and tested seven days after modeling. Evaluations included multiple cerebral infarction model assessments, neurological function scores, grip strength tests, and rotarod tests, so as to evaluate neuromotor functions. Morphological structures of brain and heart tissue were observed using hematoxylin-eosin(HE) staining, Nissl staining, and Masson staining. Network pharmacology was employed to screen the mechanisms of Naoxintong Capsules in improving multiple cerebral infarctions and myocardial injury. Neuronal and myocardial cell ultrastructures were observed using transmission electron microscopy. Apoptosis rate in brain neuronal cells was detected by TdT-mediated dUTP nick end labeling(TUNEL) staining, and reactive oxygen species(ROS) levels in myocardial cells were measured. Immunofluorescence was used to detect the expression of platelet endothelial cell adhesion molecule-1(CD31), antigen identified by monoclonal antibody Ki67(Ki67), hematopoietic progenitor cell antigen CD34(CD34), and hypoxia inducible factor-1α(HIF-1α) in brain and myocardial tissue. Western blot, and real-time quantitative polymerase chain reaction(RT-qPCR) were used to detect the expression of HIF-1α, vascular endothelial growth factor(VEGF), vascular endothelial growth factor receptor 2(VEGFR2), sarcoma(Src), basic fibroblast growth factor(bFGF), angiopoietin-1(Ang-1), and TEK receptor tyrosine kinase(Tie-2). Compared with the model group, the medium-dose group of Naoxintong Capsules showed significantly lower neurological function scores, increased grip strength, and prolonged time on the rotarod. Pathological damage in brain and heart tissue was reduced, with increased and more orderly arranged mitochondria in neurons and cardiomyocytes. Apoptosis in brain neuronal cells was decreased, and ROS levels in cardiomyocytes were reduced. The microvascular density and endothelial cells of new blood vessels in brain and heart tissue increased, with increased overlapping regions of CD31 and Ki67 expression. The relative protein and mRNA expression levels of HIF-1α, VEGF, VEGFR2, Src, Ang-1, Tie-2, and bFGF were elevated in brain tissue and myocardial tissue. Naoxintong Capsules may improve multiple cerebral infarctions and myocardial injury by mediating HIF-1α/VEGF expression to promote angiogenesis.
Animals ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Rats ; Cerebral Infarction/genetics* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Vascular Endothelial Growth Factor A/genetics* ; Capsules ; Signal Transduction/drug effects* ; Humans ; Brain/metabolism* ; Myocardium/metabolism* ; Apoptosis/drug effects*

Fritillariae Cirrhosae Bulbus is the dried bulb of perennial herbaceous plants in the Fritillaria genus(Liliaceae family) and is a representative traditional Chinese medicinal material with distinctive regional characteristics. Clinically, it is widely used in the treatment of dry cough, bronchial asthma, and other respiratory diseases, possessing significant medicinal and economic value and being highly esteemed in TCM. Currently, Fritillariae Cirrhosae Bulbus primarily relies on wild harvesting. However, due to excessive collection, its wild resources have drastically declined, and all source species have been classified as category Ⅱ in the List of National Key Protected Wild Plants, exacerbating the supply-demand imbalance in the market. To mitigate this issue, large-scale cultivation through the domestication of wild Fritillariae Cirrhosae Bulbus has become an inevitable trend. However, its strict environmental requirements, low propagation efficiency, high seedling mortality, and immature cultivation techniques have severely hindered industrialization. This study investigates the domestication process of Fritillariae Cirrhosae Bulbus, focusing on seed propagation, seedling cultivation, and medicinal material production. It also reviews the species and distribution of wild resources, their endangered status, market supply-demand dynamics, and the historical and current development of domestication. The findings indicate that enhancing propagation efficiency, optimizing cultivation models, and distinguishing between seed propagation and medicinal material production are key measures to accelerate the industrialization of domesticated Fritillariae Cirrhosae Bulbus. This research aims to promote the industrialization of Fritillariae Cirrhosae Bulbus domestication and provide a reference model for the conservation and sustainable utilization of rare and endangered medicinal plant resources.
Fritillaria/chemistry* ; Endangered Species ; Plants, Medicinal/growth & development* ; Drugs, Chinese Herbal/economics* ; China

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Objective:To investigate the diagnostic value of metagenomic next-generation sequencing (mNGS) for pyogenic spinal infections.Methods:A total of 255 patients diagnosed with pyogenic spinal infections were enrolled between September 2022 and September 2024 at Qingdao University Affiliated Hospital, Fuzhou Second General Hospital, First Affiliated Hospital of Nanchang University, Shandong University Affiliated Public Health Clinical Center, and the Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. Among them, 155 were male and 100 were female, with an average age of 62.5±14.2 years (ranging from 13 to 90 years). All patients had samples of infected tissue and/or pus collected for microbial culture and mNGS testing. The number, types, and positive rates of pathogens detected by microbial culture and mNGS were compared. Using culture results as the gold standard, receiver operating characteristic (ROC) curve analysis was performed for mNGS testing and the combined method of mNGS and microbial culture, calculating the area under the curve (AUC) and 95% CI. Results:All 255 cases were clinically diagnosed as pyogenic spinal infections, with 194 cases providing microbiological evidence. The most common Gram-positive bacterium was Staphylococcus aureus, while the most common Gram-negative bacterium was Escherichia coli. A total of 33 pathogenic microorganisms were detected by mNGS, while microbial culture detected 18 pathogenic microorganisms. The positive rate of mNGS was 72.2% (184 out of 255), which was significantly higher than that of 30.2% (77 out of 255) for microbial culture, showing a significant difference (χ 2=90.150, P<0.001); the positive rate of mNGS combined with microbial culture was 76.1% (194 out of 255) with significant difference compared to mNGS alone (χ 2=8.100, P<0.001). Among 178 culture-negative samples, the detection rate of mNGS was 65.7% (117 out of 178); among 77 culture-positive samples, the detection rate of mNGS was 87.0% (67 out of 77), and 97.0% (65 out of 67) of the detected pathogens matched the culture results at the species level. The AUCs of the ROC curves for mNGS testing and the combination of mNGS with microbial culture were 0.606 [95% CI (0.534, 0.678)] and 0.671 [95% CI (0.606, 0.736)], respectively, with significant differences compared to microbial culture ( P=0.007; P=0.007). Conclusions:mNGS demonstrates superior performance over conventional culture in identifying pathogens in pyogenic spinal infections. Moreover, combining mNGS with culture further improves diagnostic yield, supporting its integration into clinical practice.

Aim To explore the molecular mechanism of Tongluo Tangtai(TLTT)prescription in the preven-tion and treatment of diabetic peripheral neuropathy(DPN)based on network pharmacology and in vitro experimental verification.Methods The chemical composition information of Tongluo Tangtai was searched by TCMSP database and literature search,and the target of chemical composition was collected by PubChem and SwissTargetPrediction database.DPN targets were collected through GeneCards database.GO function and KEGG pathway enrichment of common target proteins were analyzed using DAVID database.The correlation network diagram was constructed using Cytoscape software,and the main active components and target genes were screened for molecular docking study.The in vitro model of DPN was constructed in Schwann cells induced by high glucose.The effect of TLTT on the survival rate of RSC96 cells was detected by CCK-8 method,and the gene expression of Wnt/β-catenin pathway related target molecules in RSC96 cells was detected by Real-time PCR.The expression levels of Wnt/β-catenin pathway-related proteins in RSC96 cells were detected by Western blot.Results The main active components such as stigmasterol,β-si-tosterol and quercetin were screened,which mainly ac-ted on EGFR,AKT1,MAPK3 and Wnt,PI3K-Akt and MAPK signaling pathways.The molecular docking re-sults showed that stigmasterol,β-sitosterol,quercetin and other components could dock well with EGFR,AKT1,MAPK3 and other targets.The results of cell experiment showed that 10％TLTT drug-containing ser-um could promote the viability of high-glucose Schwann cells,up-regulate the expression of β-catenin protein,and down-regulate the expression of GSK-3β and Wif-1 protein.Conclusions TLTT has the characteristics of multi-target-multi-pathway in the treatment of DPN.The possible mechanism is that TLTT activates the Wnt/β-catenin signaling pathway,improves the inhibi-tory effect of high glucose on the proliferation of Schwann cells,promotes the proliferation of Schwann cells,and thus improves the status of DPN.

Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Objective To explore the mechanism of matrine in the treatment of uveal melanoma by network pharmacology,and the related results were verified by molecular docking and cell experiments.Methods The potential targets of matrine were obtained from Swiss Target Prediction,SuperPred and TCMSP databases.The targets related to uveal melanoma were obtained from GeneCards,OMIM,CTD and DrugBank databases.Protein-protein interaction(PPI)network was established to screen core targets.Gene ontology(GO)enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG)signal pathway analysis were carried out for potential targets.The interaction between matrine and core targets was evaluated by molecular docking technique.The effects of different concentrations of matrine(0.25 g/L,0.50 g/L,1.00 g/L,2.00 g/L)on the proliferation of uveal melanoma cells were evaluated based on CCK-8 method.Western blot was used to verify the regulatory effects of different concentrations of matrine(0.25 g/L,0.50 g/L,1.00 g/L,2.00 g/L)on PI3K-Akt signaling pathway.Results A total of 208 potential targets of matrine were identified,and 5 453 targets related to uveal melanoma were obtained.The topological analysis of PPI network revealed 8 core targets,namely interleukin-6(IL-6),tumor necrosis factor(TNF),myelocytomatosis proteins(MYC),signal transducer and activator of transcription 3(STAT3),caspase-3(CASP3),heat shock protein 90AB1(HSP90AB1),mammalian target of rapamycin(mTOR),and matrix metalloproteinase 9(MMP9).GO enrichment analysis showed that biological processes(BP)mainly included inflammatory response,protein phosphorylation and response to exogenous stimuli;cell components(CC)mainly included plasma membrane,cell surface and cytoplasm;molecular function(MF)mainly included the same protein binding,ATP binding and kinase activity.The enrichment analysis of KEGG pathway showed that the effect of matrine was mediated by viral carcinogenesis,cancer pathway,TNF signaling pathway and PI3K-Akt signaling pathway.Molecular docking showed that matrine had good binding ability with the selected core targets.The results of cell experiments showed that matrine at concentrations of 0.50 g/L,1.00 g/L and 2.00 g/L could inhibit the proliferation of MuM2B cells,and the cell survival rate gradually decreased with the increase of concentration.Matrine at concentrations of 0.50 g/L,1.00 g/L and 2.00 g/L could down-regulate the protein expression levels of p-PI3K and p-Akt,and the protein expression levels of p-PI3K and p-Akt gradually decreased with the increase of concentration.Conclusion Matrine acts on tar-gets such as IL-6,TNF,MYC,STAT3,CASP3,HSP90AB1,mTOR,MMP9,and exerts therapeutic effects on uveal melanoma by viral carcinogenesis,cancer pathway,TNF signaling pathway and PI3K-Akt signaling pathway,etc.

Sarin(GB)is a typical representative of nerve agents with high toxicity,and very low amount can cause death.GB can cause water and atmospheric environment poisoning,so the detection of GB in water and air is of great significance.In this work,a colorimetric sensor array(CSA)based on GB inhibition of cholinesterase activity was constructed to detect GB with high selectivity.A 4×4 colorimetric array was constructed using acetylcholinesterase(AChE),butyryl cholinesterase(BuChE)and the corresponding substrate acetylthiocholine iodide(S-ACh),butyryl thiocholine iodide(S-BCh),acetylcholine chloride(ACh),butyryl choline chloride(BCh)and 2,6-dichloroindophenol ethyl ester(DCIE).The linear curve of the sensor was Y=131.3×lgC+271.6(R2=0.997),where Y was the array response Euclidean distance,C was the concentration of GB(mg/L),the linear range was 0.03?0.32 mg/L,and the detection limit was 27.6 μg/L.The method could effectively distinguish chemical warfare agents(CWA)such as VX,Soman(GD),mustard gas(HD),Louie reagent(L),and had high anti-interference ability,sensitivity and good repeatability.It was successfully applied to the detection of GB in simulated water and simulated air samples,and the sample recovery rate was 97.2% ?100.9%.This method would be potentially applied to the field rapid detection of nerve agents.

Objective To investigate the differences in oral and gut microbiota composition among children aged 3-5 years with varying body mass index(BMI)levels in Urumqi,and to provide a scientific basis for early microbiological warning and intervention strategies for childhood obesity.Methods A total of 40 children aged 3-5 years were enrolled.Based on their BMI percentiles,the participants were divided into 4 groups,including the underweight,normal weight,overweight,and obesity groups(n=10 per group).A total of 80 saliva and fecal samples were collected.Microbial community structures were analyzed using 16S rRNA gene sequencing,followed by bioinformatics and statistical analyses.Results Oral microbiota richness,as measured by Chao1 and observed-species indices,differed significantly among the four groups(P=0.004 7 and P=0.005 4,respectively),whereas no significant difference in gut microbiota diversity was observed(P>0.05).Beta diversity analysis revealed a distinct separation in oral microbiota between the normal-weight weight and other groups.At the genus level,obese children exhibited increased abundance in oral Leptotrichia,underweight children showed enrichment of gut Bacteroides,and overweight children showed increased abundance in gut Faecalibacterium and Blautia.Linear discriminant analysis effect size(LEfSe)analysis identified multiple biomarkers,including Prevotellaceae in the oral microbiota of normal-weight children,Catonella in the oral microbiota of obese children,and Clostridiales,Lachnospiraceae,and Hungatella in the gut microbiota of underweight children.Metabolic pathways related to lipopolysaccharide synthesis and amino acid metabolism were significantly upregulated in the microbiota of overweight and obese children.Conclusion Significant differences are observed in the oral and gut microbiota composition among children aged 3-5 years of different BMI levels in Urumqi.Oral microbiota show greater sensitivity to BMI changes.Specific genera,such as Catonella,Leptotrichia,and Prevotellaceae,may be involved in the development of obesity.The microbiota metabolic pathways in children with high BMI are characterized by the core features of inflammation activation and lipid metabolism dysregulation.

Objective To investigate the postoperative efficacy of laparoscopic hiatal hernia repair(LHHR)combined with Toupet or Dor fundoplication for the treatment of esophageal hiatal hernia(HH).Methods A retrospective analysis was conducted on the case data of HH patients who underwent LHHR combined with Toupet(Toupet group,n=53)and Dor(Dor group,n=53)fundoplication between December 2018 and December 2022 in Department of General Surgery of Gansu Provincial Hospital.Intraoperative and postoperative recovery outcomes of both groups were observed.We analyzed and compared the incidence of dysphagia and gastroesophageal reflux disease questionnaire(GERD-Q)scores at preoperative and postoperative intervals of 1 month,6 months,and 1 year.The incidence of postoperative complications and the 1-year recurrence rate were compared between the two groups.Additionally,factors influencing postoperative dysphagia within the first month were examined.Results The differences between the two groups in operation time,intraoperative bleeding,postoperative ventilation time,postoperative extubation time and hospitalization time were not statistically significant(P>0.05).There was no significant difference in the incidence of immediate postoperative dysphagia in two groups(P>0.05).Furthermore,the differences between the two groups in the incidence of postoperative complications,such as bloating,abdominal pain and diarrhea,were not statistically significant(P>0.05).The incidence of dysphagia in Toupet group was higher than that in Dor group at 1 month postoperatively,and the difference was statistically significant(P=0.017);but the difference in the incidence of dysphagia between the two groups at 6 months and 1 year postoperatively was not statistically significant(P=0.767,1.000).The results of binary logistic regression analysis showed that both surgical procedure(OR=2.613,95%CI 1.141-5.983,P=0.023)and esophageal contractile reserve function(OR=2.921,95%CI 1.203-7.095,P=0.018)were independent risk factors for the incidence of dysphagia in patients with HH at 1 month after surgery.Compared with the preoperative period,the GERD-Q symptom scores were lower in both groups at 1 month,6 months,and 1 year postoperatively,and the difference was statistically significant(P<0.05);but there was no statistically significant difference between the groups at the same time point(Fintergroup=0.334,P=0.565).The difference between the two groups in 1-year postoperative recurrence rates was not statistically significant(P>0.05).Conclusions LHHR combined with Toupet or Dor fundoplication are both safe and effective surgical procedures for the treatment of HH,with excellent reflux control,fewer complications and lower recurrence rates,but Toupet fundoplication is more likely to have postoperative short-term dysphagia than Dor fundoplication.